US11279760B2ActiveUtilityA1

Inhibition of cytokine-induced SH2 protein in NK cells

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Assignee: WALTER & ELIZA HALL INST MEDICAL RESPriority: Dec 16, 2015Filed: Jul 19, 2021Granted: Mar 22, 2022
Est. expiryDec 16, 2035(~9.4 yrs left)· nominal 20-yr term from priority
Inventors:Nicholas D. HuntingtonSandra E. Nicholson
A61K 35/17A61K 40/42A61K 40/15A61K 2239/57A61K 2239/55A61K 2239/49A61K 2239/46A61K 2239/38A61K 2239/31A61K 2239/48C12N 5/0646A61P 35/00A61P 35/02A61K 31/713A61K 31/506A61K 39/395A61K 2039/507A61K 38/1709A61K 2039/505C07K 16/2803A61P 31/16G01N 33/6863C07K 16/22G01N 33/566A61P 31/00C07K 16/2818A61P 31/14C07K 16/18A61K 38/04A61P 35/04A61P 31/12G01N 33/15A61P 31/22A61P 31/20Y02A50/30
76
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References
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Claims

Abstract

The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. CIS-inhibited human NK cells, wherein the CIS-inhibited human NK cells are genetically modified to have reduced expression of CIS, or are genetically modified to express a dominant negative CIS sequence variant or dominant negative fragment thereof. 
     
     
       2. The CIS-inhibited human NK cells of  claim 1 , wherein the CIS-inhibited human NK cells are NK cells genetically modified to have reduced expression of CIS. 
     
     
       3. The CIS-inhibited human NK cells of  claim 1 , wherein the CIS-inhibited human NK cells are Cish −/− . 
     
     
       4. The CIS-inhibited human NK cells of  claim 1 , in which the Cish gene has been genetically deleted. 
     
     
       5. The CIS-inhibited human NK cells of  claim 1 , wherein expression of CIS protein has been reduced by a gene silencing strategy. 
     
     
       6. The CIS-inhibited human NK cells of  claim 5 , wherein the gene silencing strategy comprises use of siRNA or RNAi. 
     
     
       7. The CIS-inhibited human NK cells of  claim 1 , wherein the CIS-inhibited human NK cells are genetically modified to express a dominant negative CIS sequence variant or dominant negative fragment thereof. 
     
     
       8. The CIS-inhibited human NK cells of  claim 1 , wherein the CIS-inhibited human NK cells are irreversibly genetically modified. 
     
     
       9. The CIS-inhibited human NK cells of  claim 1 , wherein the CIS-inhibited human NK cells are reversibly genetically modified so that over time the CIS inhibition in the NK cells decreases. 
     
     
       10. Human Cish −/+  NK cells. 
     
     
       11. Human Cish −/−  NK cells. 
     
     
       12. A composition comprising the human Cish −/−  NK cells of  claim 11 . 
     
     
       13. A pharmaceutical composition comprising the human Cish −/−  NK cells of  claim 11 .

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